Pyridine compounds having a pyridine ring such as pyridine, picoline, and lutidine are widely used as solvents, or as starting materials in various organic synthesis materials, pharmaceuticals and agrochemicals. Various processes for producing pyridine compounds are known. Representative examples of such processes include a process in which pyridine compounds are recovered from tar, as well as synthesis processes typified by the Chichibabin method.
Purification by distillation is an effective purification method of pyridine compounds. However, some impurities cannot be removed by distillation alone, and hence purification methods are the object of ongoing improvement. In particular, various methods have been disclosed as methods for removing coloring substances as well as aging coloration-causing substances.
Examples of such methods include, for instance, the following.
a method wherein distillation is performed after irradiation of a pyridine compound with UV rays (Patent Document 1);
a method wherein a pyridine compound is treated with a halogen such as chlorine, bromine, and iodine (Patent Document 2);
a method involving treatment with activated carbon after formation of a salt by a reaction with an acid (Patent Document 3);
a method that involves performing a treatment with a halogen-containing sulfur or phosphorus compound (Patent Document 4);
a method involving treatment with isocyanates (Patent Document 5);
a method involving that the addition of methanol and water followed by distillation (Patent Document 6);
a method involving contact treatment with a porous resin (Patent Document 7);
a method involving treatment with an oxide or hydroxide of an alkaline earth metal (Patent Document 8);
a method involving treatment with a solid alkali in gas phase (Patent Document 9);
a method involving treatment with a permanganate or bichromate, followed by distillation (Patent Document 10); and
a method that involves heating with metallic copper or copper oxide, followed by distillation (Patent Document 11).
The coloring substances and the aging coloration-causing substances which are removed in the above-described methods are not exactly identified. Causative agents are deemed to include amines, alcohols and/or aldehydes.
As described above, numerous methods for removing the coloring substances and the aging coloration-causing substances have been disclosed. However, the produced pyridine compound may contain impurities other than the above-described ones. Examples of such impurities include compounds having a diazine ring in which two carbon atoms of a benzene ring are substituted with nitrogen (diazine compounds) such as compounds having a pyrazine ring (pyrazine compounds), compounds having a pyrimidine ring (pyrimidine compounds) and compounds having a pyridazine ring (pyridazine compounds). No effective removal methods of these substances have been reported.
As in the case of pyridine, impurities comprising such diazine compounds are studied. Pyrazine, pyrimidine and pyridazine are impurities that are particularly likely to be problematic. Table 1 summarizes the normal boiling point and melting point of pyridine, pyrazine, pyrimidine and pyridazine
TABLE 1CompoundNormal boiling point (° C.)Melting point (° C.)Pyridine115.3−42Pyrazine11657Pyrimidine12420 to 22Pyridazine208−8
As the table shows, pyrazine and pyrimidine, in particular, have a normal boiling point close to that of pyridine, and hence separation of the foregoing cannot be achieved by simple distillation. Espacially, pyrazine and pyridine have very similar normal boiling points, and are thus difficult to separate completely, even by rectification.
Pyrazine has a comparatively strong UV absorption peak in the vicinity of 320 nm (logs in cyclohexane (328nm)=3.02, Non-patent Document 1). By contrast, pyridine lacks such a peak. If pyridine contains pyrazine as an impurity, therefore, the pyrazine exerts a significant influence on the UV absorption of pyridine. In a case where pyridine is used as a reaction starting material or a solvent, the pyrazine present as an impurity may exert likewise a significant influence.
Therefore, a demand exists for a simple and inexpensive method that allows efficiently removing diazines, in particular pyrazine and pyrimidine, from pyridine.
The above considerations apply also to other pyridine compounds. As further examples, Table 2 sets forth a comparison between the normal boiling points of methyl pyridine (picoline), methyl pyrazine, and methyl pyrimidine.
TABLE 2CompoundNormal boiling point (° C.)2-methyl pyridine128 to 1293-methyl pyridine1444-methyl pyridine1452-methyl pyrazine1354-methyl pyrimidine141 to 142
There are combinations of compounds of which the normal boiling points are close, although the normal boiling points of the combinations of the compounds are not as close as the normal boiling points of the combination of pyridine and pyrazine. Also, there is a case in which methyl pyrazine, methyl pyrimidine and so forth are contained, as impurities, in pyridine, or a case in which pyrazine, pyrimidine and so forth are contained, as impurities, in methyl pyridine. In such cases as well, separation by distillation is difficult on account of the closeness of the normal boiling points of the compounds.
As described above, the normal boiling points of pyrazine compounds and pyrimidine compounds are often close to that of pyridine compounds, and hence separation relying on distillation alone is difficult. Methods can thus be conceived that exploit differences in chemical properties, as purification methods other than distillation.
The chemical properties of pyridine compounds and diazine compounds are well researched. Pyridine and pyrazine exhibit the following features.
Both pyridine and pyrazine undergo nucleophilic substitution reactions, on carbon atoms, with NaNH2 or the like, to yield amino pyridine and amino pyrazine, respectively.
With alkyl halides, pyridine and pyrazine undergo electrophilic reactions on nitrogen atoms, to yield N-alkyl pyridinium and N-alkyl pyrazinium, respectively.
Both pyridine and pyrazine are oxidized by hydrogen peroxide or the like to yield a corresponding N-oxide. As regards reduction, pyridine and pyrazine yield piperidine and piperazine, respectively, when fully reduced.
It has been reported that pyridine reacts with lithium aluminum hydride to yield dihydropyridyl complexes of aluminum (Non-patent Documents 2 and 3).
Patent Document 1: Japanese Examined Patent Publication No. S43-15977
Patent Document 2: Japanese Examined Patent Publication No. S43-20187
Patent Document 3: Japanese Examined Patent Publication No. S43-21545
Patent Document 4: Japanese Examined Patent Publication
No. S46-11502
Patent Document 5: Japanese Examined Patent Publication No. S52-951
Patent Document 6: Japanese Examined Patent Publication No. S54-34736
Patent Document 7: Japanese Examined Patent Publication No. S60-19294
Patent Document 8: Japanese Patent Application Publication No. S60-215670
Patent Document 9: Japanese Examined Patent Publication No. H6-746
Patent Document 10: Japanese Examined Patent Publication No. H6-45597
Patent Document 11: Japanese Patent Application Publication No. 2001-199960
Non-patent Documents
Non-patent Document 1: Comprehensive Heterocyclic Chemistry, Vol. 3, Part 2B, Pergamon Press, 1984
Non-patent Document 2: Dennis D. Tanner and Chi-Ming Yang, J. Org. Chem. 1993, 58, 1840-1846
Non-patent Document 3: Karl Hensen et al., Inorg. Chem. 1999, 38, 4700-4704